Normal Lab Values

Neoplasia

Readings from Robbins Basic Pathology, 11th ed.  
PAGES TOPICS  
186 - 230 Neoplasia (entire chapter)  
233 - 234 Laboratory Diagnosis of Cancer  

Website Cases:

Additional cases (NOT assigned):

Gross specimen videos:

Organ Diagnosis Video
Uterus Leiomyoma Video
Colon Familial Adenomatous Polyposis Video
Lung Primary carcinoma of the lung Video
Lung Metastatic carcinoma Video
Liver Primary hepatocellular carcinoma Video
Liver Metastatic carcinoma Video
Uterus Endometrial carcinoma Video
Uterus Cervical carcinoma Video

 

CASE NUMBER 155
[DigitalScope]


--Click here for a video debrief of the pathology findings presented in this case--

Clinical History: A 72-year-old man with a 5-year history of dementia was admitted to the hospital from a nursing home with fever, mental status changes and productive cough. He was diagnosed with bronchopneumonia and treated with antibiotics, but died in the hospital. The gross and Summary of Microscopic Findings provided are of an incidental finding at autopsy.

Image Gallery:

Summary of Gross Findings
In the right lobe of the liver there was a circumscribed, dark red, spongy mass 4 cm in size. In the center of the mass there was a gray, firm, fibrous core.
Summary of Microscopic Findings
Inspection reveals a mass with many blood filled spaces. These are formed by anastomosing strands of connective tissue, partially hyalinized, lined by endothelial cells. Notice the subcapsular location of the tumor and its relationship to the liver parenchyma.
Review Liver Histology
Slide 3: Liver
[DigitalScope]

The liver is the organ that metabolizes nutrients received from the digestive tract. These nutrients and processed by tissue hepatocytes which are large polygonal cells. The hepatocyes are separated by portal triads. The triads consist of an artery, a vein and a bile duct. The bile duct is lined by cuboidal epithelium. The artery has a muscular wall and a flat endothelial lining. The sinuses are well defined and contain a small amount of blood.

Gross image questions:

  • Describe the gross appearance of the lesion in the liver. Does it appear circumscribed or infiltrative?

    --ANSWER--
    The gross appearance of the lesion (seen on the far right side of the specimen) appears dark red and is well-circumscribed.

VM image questions:

  • Describe the histologic findings. Does the lesion appear circumscribed or infiltrative?
  • Do you see necrosis, pleomorphism/cytologic atypia or mitotic figures?
  • Identify in an annotated image an endothelial cell in the lesion.
  • Find a nerve, a portal triad and a central vein.
  • What is the overall microscopic appearance of the liver?
    --ANSWER--
    The lesion itself is well circumscribed and exhibits very little necrosis, atypia, or mitotic figures. The image below shows a nerve seen within the lesion.

Differential Diagnosis:

155-1a. What is the differential diagnosis?

155-1b. Based on the histologic findings?

155-1c. What is the final diagnosis and why?

--ANSWER--

 

155-2. Which of the following features is most suggestive of benignancy in a neoplasm?

  1. Circumscription
  2. High mitotic rate
  3. Multifocal disease
  4. Necrosis
  5. Nuclear pleomorphism

--ANSWER--

 

 

155-3. Which of the following is the correct term for a malignant tumor that shows this same type of differentiation?

  1. Adenoma 
  2. Adenocarcinoma 
  3. Carcinoma 
  4. Choristoma 
  5. Cystadenoma 
  6. Hamartoma 
  7. Leukemia 
  8. Lymphoma 
  9. Papilloma 
  10. Polyp 
  11. Sarcoma 
  12. Squamous cell carcinoma 
  13. Teratoma

--ANSWER--

 

 

155-4. Malignant tumors in the liver that show this type of differentiation are associated with exposure to which of the following?

  1. Asbestos
  2. Benzene
  3. Beryllium 
  4. Cadmium 
  5. Vinyl chloride

--ANSWER--

 

 

CASE NUMBER 505
[DigitalScope]

--Click here for a video debrief of the pathology findings presented in this case--

Clinical History: A 25-year-old man presented to his primary care physician following an episode of hematochezia. He reports that his mother died of colon cancer at the age of 47. Colonoscopy reveals over 100 polyps ranging in size from 5 to 15 mm. A biopsy of one of the polyps was performed and microscopic images are provided. The patient subsequently underwent total colectomy.

Image Gallery:

Summary of Gross Findings
Hundreds of polypoid masses are seen throughout the colon.
Summary of Microscopic Findings
The exophytic structure of the polyp can be seen with the naked eye. There is a short stalk lined by normal colon mucosa with blood vessels in the submucosa. The finger-like villi of the polyp are lined by adenomatous mucosa, the hallmark of a neoplastic polyp. Compared to the nearby normal mucosa, the nuclei are elongated, hyperchromatic and stratified. There is increased nuclear to cytoplasmic ratio and decreased cytoplasmic mucin.
Review Colon Histology
Norm No. 27 Colon
[DigitalScope]

The colon is lined by glandular epithelium with numerous mucin secreting goblet cells. The epithelium is infolded into straight tubular glands of uniform diameter to increase the surface area available for secretion and absorption.

Gross image question:

  • Describe the appearance of the gross specimen.

VM image questions:

  • Describe the microscopic appearance of the biopsied polyp.
  • Is normal colonic mucosa present?
  • Identify an area of dysplasia using high power.
  • How can you differentiate dysplastic epithelium from normal epithelium?
  • Is the resection margin free of dysplasia?

Differential Diagnosis:

505-1a. What is the differential diagnosis?

505-1b. With the addition of the family history?

505-1c. Based on the colonoscopy findings?

505-1d. What is the final diagnosis and why?

 

--ANSWER--

     

505-2. What of the following is the most appropriate term for the lesion shown in the histologic section?

  1. Adenoma
  2. Carcinoma
  3. Choristoma
  4. Hamartoma
  5. Sarcoma

--ANSWER--

 

 

505-3. Which of the following is the correct term for the epithelial morphology in this lesion?

  1. Anaplastic
  2. Carcinoma in situ
  3. Dysplastic
  4. Inflamed
  5. Reactive

--ANSWER--

 

 

505-4. Mutational analysis would most likely show a mutation in which of the following genes?

  1. APC
  2. LKB1/STK11
  3. MLH1
  4. MSH2
  5. PTEN

--ANSWER--

 

 

505-5. Which of the following genetic abnormalities is most likely to be the etiology of this patient’s disease?

  1. Autosomal dominant mutation
  2. Autosomal recessive mutation
  3. Genomic imprinting
  4. Germline mosaicism
  5. Random X inactivation

--ANSWER--

 

 

505-6. Which of the following is the recommended treatment for patients with this disease?

  1. Daily NSAIDs
  2. Endoscopic surveillance every 6 months
  3. Endoscopic surveillance every year
  4. Endoscopy for symptomatic cases only
  5. Prophylactic colectomy

--ANSWER--

CASE NUMBER 233
[DigitalScope]

--Click here for a video debrief of the pathology findings presented in this case--

Clinical History: A 45-year-old woman presented to her gynecologist for her first Pap test (shown below). Clinical history revealed that she had been sexually active since the age of 14 and had used oral contraceptives for birth control. She has had no previous Pap tests. Physical exam revealed a fungating mass at the cervical os with thickening of the adjacent upper vaginal wall. The clinician also noted that the cervix was enlarged and felt firm. Following a biopsy, the patient underwent a hysterectomy with bilateral salpingo-oophorectomy. 

Image Gallery:

Summary of Gross Findings
The entire external cervix showed a large, gray-pink, fungating lesion, 5.5 cm in size. It extended into the internal cervical canal and also involved one of the obturator lymph nodes.
Summary of Microscopic Findings
The external cervix shows fibrosis and acute and chronic inflammatory infiltration. A portion of the cervical mucosa is infiltrated with squamous cell carcinoma. The tumor cells are pleomorphic and bizarre and frequently form giant cells. Strands and nests of the tumor cells are seen in the cervical stroma. Marked acute and chronic inflammation is present in association with the tumor.
Review Cervix Histology
Slide 249 (cervix, H&E) [DigitalScope]
UCSF slide 405 (cervix, trichrome) [DigitalScope]

The uterine cervix shown in slide 249 is continuous with both the body of the uterus and the upper portion of the vagina. Note that the wall has considerable smooth muscle and much dense connective tissue. Note also the number of collagen fibers in the stroma.

The mucosa is lined by a tall columnar mucus-secreting epithelium in its uterine portion, but note the abrupt change to stratified squamous epithelium at its vaginal face. This stratocolumnar junction which should be readily identifiable in both slide 249 [example] and UCSF slide 405 [example] is frequently the site of pre-neoplastic and neoplastic (cervical cancer) changes. The mucosa is thrown into deep irregular folds known as plicae palmitae (palmate folds). During the majority of the uterine cycle these glands secrete a highly viscous mucus forming a barrier to microorganisms, while at mid-cycle (ovulation) the mucus becomes more hydrated, which facilitates sperm entry. Blockage of the openings of the cervical mucosal glands frequently results in the accumulation of secretory products within the glands, leading to the formation of dilated Nabothian cysts which may be seen in USCF slide 405 [example]. These cysts are generally benign; however, they can become clinically relevant should they become enlarged enough to cause obstruction of the cervical canal.

Lab image questions:

  • For the Pap test, identify: atypical cells, normal squamous cells, and several neutrophils.

Gross image questions:

  • For the gross specimen, identify the tumor, the endometrium, the myometrium and the two ovaries with fallopian tubes.
VM image questions:
  • For the histologic section, identify: invasive carcinoma, koilocytic change, desmoplasia, a keratin pearl and a mitotic figure.
  • Is this a mitotically active tumor?
  • Where in the uterus did this section come from (i.e. body, fundus, cervix)?
  • Identify an area of tumor necrosis.
  • What does this tell you about the tendency of invasive squamous cell carcinoma to be cystic?

Differential Diagnosis:

233-1a. What is the differential diagnosis based on the Pap test?

233-1b. Based on the clinical findings?

233-1c. What is the final diagnosis and why?

--ANSWER--

 

233-2. Which of the following is a risk factor in the development of this disease?

  1. AIDS
  2. Early age at menarche
  3. History of endocervical polyps
  4. Low parity
  5. Obesity

--ANSWER--

 

233-3. Which of the following viruses is most closely associated with the development of this disease?

  1. HPV-1
  2. HPV-2
  3. HPV-4
  4. HPV-6
  5. HPV-11
  6. HPV-16

--ANSWER--

 

233-4. Which of the following is the proposed mechanism for the oncogenicity of this virus?

  1. CagA initiates a signaling cascade
  2. Chronic inflammation
  3. E7 binds RB, releasing E2F transcription factors
  4. LMP activates BCL2
  5. TAX represses CDKN2A/p16 and TP53

--ANSWER--

 

 

CASE NUMBER 511 - slide courtesy of UIowa
[DigitalScope]

--Click here for a video debrief of the pathology findings presented in this case--

Clinical History: A 69-year-old woman presented to her primary care physician with a six-month history of anorexia and weight loss of ten pounds. Clinical history was relevant for a 60-pack-year smoking history and a 5-year history of hypertension and obstructive pulmonary disease. Routine laboratory tests revealed a serum calcium of 12.8 mg/dl (normal 8.6-11.1). A chest CT was performed, followed by a biopsy.

Image Gallery:

Summary of Radiologic Findings
The first image is a contrast-enhanced CT of the chest that shows a large mass in the left lung and left hilum. The second image is a CT of the abdomen that shows multiple lucent lesions consistent with metastatic carcinoma.
Summary of Microscopic Findings
The section shows a well differentiated squamous cell carcinoma arising within the bronchial mucosa and invading into the surrounding soft tissue, including direct invasion into bronchial cartilage. The carcinoma is composed of large cells with abundant eosinophilic cytoplasm. The malignant squames are shed into the bronchial lumen; cytologic examination of bronchial material can be diagnostic. The carcinoma extends into the surrounding soft tissue in sharp tongues of cells that provoke a desmoplastic response. The bronchial cartilage shows exuberant reactive changes. Alveolar tissue is present at the upper right of the slide.
Review Lung Histology
Slide No. 24 Lung
[DigitalScope]

The primary function of the lung is gas exchange. Therefore, alveoli have thin walls lined by thin flat pneumocytes and endothelial cells. There is no thickening or fibrosis of the interstitium. The bronchioli are lined with basally oriented ciliated columnar epithelium. The bronchi are lined by similar epithelium. There are mucous glands within the submucosa. The bronchial smooth muscle is not hypertrophied. The pulmonary vessels are patent with no evidence of intimal thickening or muscular hyperplasia.

Review Liver Histology
Slide 3: Liver
[DigitalScope]

The liver is the organ that metabolizes nutrients received from the digestive tract. These nutrients and processed by tissue hepatocytes which are large polygonal cells. The hepatocyes are separated by portal triads. The triads consist of an artery, a vein and a bile duct. The bile duct is lined by cuboidal epithelium. The artery has a muscular wall and a flat endothelial lining. The sinuses are well defined and contain a small amount of blood.

VM questions:

  • Screen shot and annotate 1) areas of normal lung 2) cartilage and bronchial seromucinous glands, 3) an area of in situ carcinoma and other areas of invasive carcinoma.
  • Make note of the morphologic features you see that help you classify this neoplasm.

Differential Diagnosis:

511-1a. What is the differential diagnosis based on the patient’s initial presentation and clinical history?

511-1b. What does the hypercalcemia suggest?

511-1c. What is your differential diagnosis based on the CT findings?

511-1d. What is your final diagnosis and why?

--ANSWER--


511-2. Which of the following is the most likely etiology of this patient’s hypercalcemia?

  1. ACTH
  2. Atrial natriuretic hormone
  3. Erythropoietin
  4. Parathyroid hormone-related protein
  5. Serotonin

--ANSWER--

 

 

511-3. Which of the following is most commonly associated with hypoglycemia?

  1. Carcinoma of the breast
  2. Gastric carcinoma
  3. Hepatocellular carcinoma
  4. Pancreatic carcinoma
  5. Thymoma

--ANSWER--

 

 

511-4. Following evaluation of the patient’s CT scan, a PET scan is performed that shows that the lesion is extremely avid for 18F-fluorodeoxyglucose. Which of the following features of cancer accounts for this finding?

  1. Epigenetic changes
  2. Gene amplification
  3. Genomic instability
  4. Matrix metalloproteinase activity
  5. Warburg effect

--ANSWER--

 

511-5. The patient refuses treatment. Over the next 4 weeks, her weight decreases rapidly and she becomes weak and easily fatigued. Laboratory tests show a hemoglobin of 9 g/dl (normal 12 – 15.5 g/dl). Which of the following is the most likely cause of this patient’s cachexia?

  1. Autoantibodies
  2. Bradykinin
  3. Transforming growth factor alpha
  4. Tumor antigens
  5. Tumor necrosis factor

--ANSWER--

 

 

 

CASE NUMBER 253
[DigitalScope]

--Click here for a video debrief of the pathology findings presented in this case--

Clinical History: A 60-year-old woman was referred to a gastroenterologist due to a one-year history of weight loss with new onset abdominal pain. Physical exam revealed occult blood present in her stool. Upper endoscopy showed a fungating, ulcerated mass in the gastric antrum and the patient underwent a partial gastrectomy. Gross and microscopic images are provided.

Image Gallery:

Summary of Gross Findings
The resected portion of the stomach showed a large fungating, partially ulcerated tumor mass in the antrum. Regional lymph nodes and a liver biopsy were free of tumor.
Summary of Microscopic Findings
There is a rather abrupt change of the normal stomach mucosa to malignant tumor tissue, projecting into the lumen as a cauliflower-like mass. The tumor forms abundant irregular acini, lined by one or more layers of atypical cells with mostly large irregular nuclei and poorly defined eosinophilic cytoplasm. Atypical mitoses are moderately frequent. The tumor has infiltrated through the muscularis mucosa and the edematous submucosa and has invaded the muscle layers. The invading tumor had elicited a rather marked neutrophilic and plasma cell response.
Review Stomach Histology
Slide 16 Stomach, fundus
[DigitalScope]

The normal gastric mucosa of the fundus contains superficial fovea arranged in leaf like fronds and deeper gastric glands. The foveolar cells secrete mucin. The gastric glands include mucous cells, parietal cells, chief cells and enteroendocrine cells.

Gross image questions:
Screenshot and annotate the area of abnormality you observe. Describe the findings and the differential based on these gross features.

VM image questions:

  • Screenshot and annotate at low magnification:
    1. the luminal and serosal surfaces of the stomach,
    2. an area of “near normal” stomach,
    3. an example of intestinal metaplasia, and
    4. areas diagnostic for what this patient has presented with.
  • Describe the features that help you secure the diagnosis in this case.

Differential Diagnosis:

253-1a. What is the differential diagnosis based on the patient’s initial presentation?

253-1b. Based on the physical exam?

253-1c. What is the final diagnosis based on the gross and microscopic images and why?

--ANSWER--

 

253-2. Which of the following risk factors has the most significant association with gastric cancer?

  1. Chronic excess alcohol use
  2. Chromium
  3. Cigarette smoking
  4. Helicobacter pylori infection
  5. Human papilloma virus infection

--ANSWER--

 

 

253-4. Several years later, the patient’s stomach is rebiopsied and a diagnosis of MALT lymphoma is rendered. Which of the following is the most likely etiology of this disease?

  1. Altered cell surface glycolipids and glycoproteins
  2. Downregulation of NF-kB
  3. Elaboration of PTHRP by gastric epithelial cells
  4. MYC amplification
  5. Stimulation of B cells by H.pylori-reactive T cells

--ANSWER--

 

 

 

CASE NUMBER 134
[DigitalScope]

--Click here for a video debrief of the pathology findings presented in this case--

Clinical History: An 81-year-old asymptomatic woman was found to have guaiac-positive stool during a routine exam at her nursing home.  Flexible sigmoidoscopy revealed a fungating mass and she underwent a partial colectomy. Gross and microscopic images are provided.

Image Gallery:

Summary of Gross Findings
A 4 cm fungating, centrally ulcerated mass was found on gross examination.
Summary of Microscopic Findings
This section, which includes the edge of the tumor shows invasive adenocarcinoma arising in a villous adenoma. Tall villi lined by neoplastic epithelium replace the normal mucosa at the edge of the mass. Irregular glandular spaces are lined by tumor cells and large pools of mucin are seen, as well as desmoplastic (fibrotic) stroma. Although the nuclei of the carcinoma are anaplastic when compared to the normal colon mucosa, the neoplastic epithelium retains a columnar appearance, typically seen in colon carcinoma.
Review Colon Histology
Norm No. 27 Colon
[DigitalScope]

The colon is lined by glandular epithelium with numerous mucin secreting goblet cells. The epithelium is infolded into straight tubular glands of uniform diameter to increase the surface area available for secretion and absorption.

Gross image questions:
Screenshot and annotate the gross image showing 1) normal colonic mucosal surface, 2) pericolic adipose tissue, 3) the abnormal area of mucosa you observe.

VM image questions:
Screenshot and annotate:

  1. an area of normal to abnormal colonic mucosa
  2. a cluster of atypical cells at high magnification
  3. describe the abnormal architectural and cytologic features you see and your differential diagnosis
  4. an area of stromal invasion, if present.

Differential Diagnosis:

134-1a. What is the differential diagnosis based on the patient’s initial presentation?

134-1b. Following endoscopy?

134-1c. What is the final diagnosis and why?

 

--ANSWER--

     

     

134-2. In this clinical setting, which of the following features distinguishes carcinoma from dysplasia?

  1. Brisk mitotic activity
  2. Degree of nuclear pleomorphism
  3. Invasion
  4. Presence of large nucleoli
  5. Ratio of dysplastic cells to normal cells

--ANSWER--

 

134-3. In this tumor, the APC gene is commonly mutated. Which of the following terms best describes APC?

  1. DNA repair gene
  2. Regulator of cell cycle
  3. Telomerase
  4. Tumor oncogene
  5. Tumor suppressor gene

--ANSWER--

 

134-4. Which of the following features is included in the determination of tumor stage in this disease?

  1. Degree of nuclear pleomorphism
  2. Loss of polarity
  3. Lymph node involvement
  4. Number of mitotic figures
  5. Surface ulceration

--ANSWER--

 

NEOPLASIA Review Items

Key Vocabulary Terms

adenoma exophytic  oncology
anaplasia grade papilloma
angiogenesis hamartoma paraneoplastic syndrome 
aplasia  heterotopia parenchyma
atrophy hyperplasia Philadelphia chromosome
benign hypertrophy pleomorphism
borderline malignancy hypoplasia point mutation 
cachexia in situ polyp
cancer initiation premaligant
carcinogen intraepithelial prognosis
carcinoid invasion progression
carcinoid syndrome leukoplakia promotion
carcinoma low malignant potential proto-oncogene
carcinosarcoma malignant sarcoma
cystadenocarcinoma  medullary scirrhous
cystadenoma metastasis serous  
dermoid microinvasion stage 
desmoid mixed tumor tumor  
desmoplasia mucinous tumor associated antigen
differentiation neoplasia tumor marker
DNA repair gene occult malignancy tumor specific antigen
dysplasia oncogene tumor suppressor gene
endophytic    

Regarding "oncogenes" and "tumor suppressor genes:"

Oncogenes are a general class of genes that, when mutated, permit or induce uncontrolled cellular proliferation and malignant change.

Oncogenes are further classified as either protooncogenes OR tumor suppressor genes (anti-oncogenes). Protooncogenes encode proteins that stimulate DNA synthesis and cell division, including peptide growth factors and their cellular membrane receptors; second-messenger cascade proteins, which transmit information from cell membrane to nucleus; and nuclear transcription factors, which control gene expression by binding to DNA. Conversion of a protooncogene to an oncogene by amplification, translocation, or point mutation can lead to unrestrained cellular proliferation and malignant change. Only 1 copy (allele) of a protooncogene need undergo mutation to induce tumor formation. Protooncogenes are not involved in inherited cancer syndromes, with the exception of the RET protooncogene in multiple endocrine neoplasia.

Tumor suppressor genes (antioncogenes), which encode proteins that normally serve to restrain cell proliferation, can be inactivated by point mutation, deletion, or loss of expression. An inherited mutation in 1 copy of a tumor suppressor gene is the basis of most familial predispositions to cancer. Malignant cellular proliferation does not occur until the remaining, functional copy of the gene is inactivated by mutation or by deletion of part or all of its chromosome. In a person born with two normal copies of a tumor suppressor gene, both must be inactivated by mutation before tumor formation occurs. BRCA1 and BRCA2, which predispose to familial early-onset breast cancer and ovarian cancer, are tumor suppressor genes.

LEARNING OBJECTIVES

Goal 1: Genetic Basis of Neoplasia
Apply knowledge of the genetic basis of neoplasia to explain how genetic changes are acquired; how functional alterations in these mutated genes lead to the development of cancer; and how these alterations can be exploited with therapy.

  • Objective1: Genetic Mechanisms of Neoplasia
    Compare and contrast molecular genetic mechanisms that underlie cancers discussing, with examples, the role of germline mutations; somatic mutations including point mutations, deletions, amplifications and translocations; and epigenetic changes.
  • Objective 2: Oncogenes and Tumor Suppressor Genes
    Explain the action of oncogenes and tumor suppressor genes in growth factor- initiated signal transduction in both normal and neoplastic cells, and discuss how this information can be utilized for treatment.
  • Objective 3: Genes that Promote Growth or Inhibit Cell Death
    Compare and contrast the actions of genes that promote cell growth in cancers with those that inhibit cell death and explain how this information influences the choice of therapeutic agents.
  • Objective 4: DNA Fidelity
    Describe how cells maintain DNA fidelity and discuss, with examples, how mutations in these pathways produce genomic instability and clonal evolution.

Goal 2: Characteristics of Neoplasia
Apply knowledge of the characteristics of neoplasia to discuss the morphologic appearance, classification, biological behavior and staging of neoplasms.

  • Objective 1: Morphologic Features of Neoplasia
    Describe the essential morphologic features of neoplasms and indicate how these can be used to diagnose, classify and predict biological behavior of cancers.
  • Objective 2: Cellular Capabilities of Neoplasia
    Discuss the cellular capabilities of neoplasms that enable them to invade tissues and to metastasize, and recognize how this differentiates benign from malignant neoplasms.
  • Objective 3: Stromal Elements in Cancer
    Discuss the dependence of cancers on stromal elements and explain how this information can be used to treat cancers.
  • Objective 4: Paraneoplastic Syndromes
    Define and provide examples of paraneoplastic syndromes, and describe how substances produced by cancers can produce systemic effects in the host.

 

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